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Abstract
Objective: To examine sex differences in the relationship between clinical symptoms related to Alzheimer disease (AD) (verbal memory deficits) and neurodegeneration (hippocampal volume/intracranial volume ratio [HpVR]) across AD stages.
Methods: The sample included 379 healthy participants, 694 participants with amnestic mild cognitive impairment (aMCI), and 235 participants with AD and dementia from the Alzheimer's Disease Neuroimaging Initiative who completed the Rey Auditory Verbal Learning Test (RAVLT). Cross-sectional analyses were conducted using linear regression to examine the interaction between sex and HpVR on RAVLT across and within diagnostic groups adjusting for age, education, and APOE ε4 status.
Results: Across groups, there were significant sex × HpVR interactions for immediate and delayed recall (p < 0.01). Women outperformed men among individuals with moderate to larger HpVR, but not among individuals with smaller HpVR. In diagnosis-stratified analyses, the HpVR × sex interaction was significant in the aMCI group, but not in the control or AD dementia groups, for immediate and delayed recall (p < 0.01). Among controls, women outperformed men on both outcomes irrespective of HpVR (p < 0.001). In AD dementia, better RAVLT performance was independently associated with female sex (immediate, p = 0.04) and larger HpVR (delayed, p = 0.001).
Conclusion: Women showed an advantage in verbal memory despite evidence of moderate hippocampal atrophy. This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages.
GLOSSARY
- AD=
- Alzheimer disease;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- aMCI=
- amnestic mild cognitive impairment;
- CDR=
- Clinical Dementia Rating;
- HpVR=
- hippocampal volume/intracranial volume ratio;
- MCI=
- mild cognitive impairment;
- MMSE=
- Mini-Mental State Examination;
- RAVLT=
- Rey Auditory Verbal Learning Test
Footnotes
Coinvestigators are listed on the Neurology® Web site at Neurology.org.
Data used in this study were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu). Hence, with the exception of Susan Landau, investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or preparation of this manuscript.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 1364
Supplemental data at Neurology.org
- Received August 4, 2015.
- Accepted in final form October 26, 2015.
- © 2016 American Academy of Neurology
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